Malaria remains one of the most important global health challenges, with an estimated 3 billion people at risk of infection, leading to approximately 250 million cases and 1 million deaths each year. The greatest burden of malaria, by far, remains in the heartland of Africa, characterized by large contiguous areas of high transmission, low coverage of proven control interventions, and limited Infrastructure to monitor trends in malaria burden and measure the impact of interventions. The overall purpose of this program will be to establish an International Center of Excellence In Malaria Research in Uganda and perform comprehensive surveillance studies aimed to improve understanding of the disease and measure the impact of population-level control interventions. Uganda provides an ideal environment for this program, where malaria covers a wide range of epidemiological settings. Studies will be conducted in six sentinel sites, ranging from areas of relatively low transmission intensity to areas with some of the highest transmission intensities recorded in the world. Our comprehensive approach to surveillance will bring together expertise from multiple disciplines to collect data across multiple levels, reflecting the complex nature of interactions between the mosquito vector, malaria parasite and human host. The program will consist of 4 research projects linked together in an integrated manner to maximize scientific discovery. Research project 1 will compare different malaria surveillance methodologies and measure the impact and cost-effectiveness of control interventions. Research project 2 will use a modeling approach to evaluate the optimal suites of malaria control interventions in different transmission settings. Research project 3 will investigate the role of immunological assays for estimating transmission intensity and predicting disease risk. Research project 4 will identify markers of antimalarial drug and insecticide resistance and investigate the role of these markers as malaria surveillance tools. In addition to the research activities described, this program will place a strong emphasis on local training and capacity building, the transfer of technology, and building strong relationships between researchers and policy makers.